This proposal is submitted in response to RFA-DA-08-022. Our overall goal is to develop a multidisciplinary P20 research center that conducts basic science and clinical research on the neurobiology and molecular mechanisms of prescription drug abuse. Although addiction to prescription drugs and illicit drugs has many similar features, prescription drug abuse in the setting of legitimate medical use is a unique form of drug addiction that remains to be investigated. Indeed, significant concerns over prescription drug abuse have grown over recent years. Therefore, establishing a translational research center entirely dedicated to this line of research will be novel, timely and clinically relevant. In the scientific research plan of the proposed P20 center, we will study neuroimaging and molecular mechanisms of addiction to opioid analgesics and its interaction with clinical and experimental pain. Three specific aims will be proposed for the overall research plan: 1) to examine behavioral and neuroimaging changes in relation to the interaction between pain and opioid addiction in human subjects and rodents, 2) to explore the role of the brain dopaminergic system in the interaction between pain and opioid addiction, and 3) to investigate the molecular mechanisms underlying the functional role of brain dopamine receptors in the interaction between pain and opioid addiction. The data generated from this research plan will provide novel information on the neural and molecular mechanisms of opioid addiction and its interaction with clinical pain. The operational plan of this P20 center will include both short-term and long-term goals. The short-term goals of this P20 center are to 1) develop and consolidate infrastructures, 2) foster interdisciplinary, collaborative basic science and clinical research, and 3) generate scientific data according to proposed specific aims. The long-term goals are to 1) prepare logistic and administrative needs for the future P50 research center and 2) generate preliminary data for future studies under the P50 research center. The successful implementation of the research and operational plan outlined for this P20 center will lead to the formation of a multidisciplinary P50 research center with expanded research objectives to study the clinical neurobiology and molecular mechanisms of prescription drug abuse.